The public cemetery was established in 1801 using the pre-existing structure of the Certosa di San Girolamo di Casara, founded in the middle of the 14th century that was closed by Napoleon in 1797. The passion of the local nobility and aristocracy for monumental family tombs transformed the Certosa in an "open air museum," a stage of the Italian grand tour: it was visited by Byron, Dickens, Theodor Mommsen, and Stendhal. In particular the third cloister (or that of the Chapel) is noteworthy a tour of neoclassicisminspired structures with simbology from the age of enlightenment. Some tombs are painted in tempera, others are made of stucco and scagliola.

An aspect that distinguishes the Certosa of Bologna from other monumental cemeteries of Europe is derived from the complex articulation of its use of space. To the original convent nucleus were added lodges, rooms, and porticos that recreate glimpses of a setting that recalls the city of the "living". Even the porticoed eastern entrance of the cemetery, which is linked to the one that leads to the Sanctuary of San Luca with only a small break, creates the continuity between necropolis and city.

The discovery of an Etruscan necropolis during archeological excavations organized by the engineer Antonio Zannoni in order to extend the cemetery at the end of the 19th century are now in the Civic Archeological Museum of Bologna.